New Guidance to Optimize Antipsychotic Treatment

Batya Swift Yasgur, MA, LSW

May 28, 2020

A new consensus statement recommends monitoring antipsychotic blood levels, also known as therapeutic drug monitoring (TDM), to inform treatment decisions and optimize safety and efficacy.

The statement, jointly authored by experts from the American Society of Clinical Psychopharmacology (ASCP) and the Germany-based Therapeutic Drug Monitoring Task Force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie, recommends antipsychotic TDM, particularly for specific patient groups and for patients with suspected nonadherence.

"This [TDM] is a valuable and reliable instrument for personalizing treatment, which is an increasing focus today — individualizing and tailoring pharmacotherapy," lead author Georgios Schoretsanitis, MD, PhD, Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, and Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York, told Medscape Medical News.

"I am particularly satisfied to say that this paper adds much knowledge and is a holistic approach, focusing not only on theoretical knowledge but also aiming to make the life of clinicians easier, providing more of an algorithm and decision-making instrument for clinical use in everyday clinical scenarios and problems related to antipsychotic treatment," he added.

The study was published online May 19 in the Journal of Clinical Psychiatry.

Problem-Solving Tool

"The therapeutic reference range for antipsychotic levels in blood consists of a lower limit, below which therapeutic response is relatively unlikely, and an upper limit, above which ADRs [adverse drug reactions]…are more likely to occur," the authors write.

TDM can determine whether a patient has a subtherapeutic antipsychotic blood concentration and may explain a lack of response or a supra-therapeutic concentration, which could be associated with adverse drug reactions.

"It is important for clinicians to realize that this type of monitoring is not equally indicated for all antipsychotics and not planned as a way of providing insight if there are no questions. In other words, it is a problem-solving tool for a problem, a complicated situation, or a challenging scenario you’re trying to solve," Schoretsanitis said.

The authors divide their recommendations regarding routine TDM for antipsychotics into four categories, based on level of evidence.

Strongly recommended (Level 1)

 

·      Clozapine

·      Fluphenazine

·      Haloperidol

·      Olanzapine

·      Perazine

·      Perphenazine

Recommended (Level 2)

·      Aripiprazole

·      Chlorpromazine

·      Flupentixol

·      Paliperidone

·      Quetiapine

·      Risperidone

·      Sertindole

·      Ziprasidone

Useful (Level 3)

·      Brexpiprazole

·      Cariprazine

·      Chlorprothixene

·      Iloperidone

·      Loxapine

·      Lurasidone

·      Melperone

·      Pimozide

Potentially useful (Level 4)

·      Asenapine

Proven Benefits

"We tried to narrow down specific situations and scenarios in which TDM can be useful and, in fact, has proven benefits," said Schoretsanitis.

Patients who have no clinical response, even within established dose ranges, who have a recurrence or relapse during maintenance treatment, or who have ADRs are candidates for TDM.

Patients receiving polypharmacy can benefit from TDM because some coprescribed medications can raise or lower antipsychotic blood levels via overlapping metabolic pathways.

Additional populations requiring TDM are elderly patients, pregnant/lactating women, patients with medical comorbidities such as renal or hepatic disease, children/adolescents, patients with intellectual disabilities, and forensic or court-mandated patients.

Schoretsanitis noted that switching between formulations — for example from an oral to a long-acting injectable antipsychotic (LAI) — can "easily be guided by regular use of TDM," as can switching from a brand name drug to a generic.

Patients with acute inflammatory conditions, such as COVID-19, "are good candidates for TDM, even with drugs that were previously well-tolerated, because inflammation affects the way the body metabolizes drugs, leaving patients at high risk for developing toxicity," he added.

"The most common scenario for using TDM in clinical practice is to measure adherence to antipsychotics, since TDM is one of the most reliable ways to assess adherence and thereby prevent relapse or recurrence of the disease," said Schoretsanitis.

Long Overdue

Sheldon Preskorn, MD, professor of psychiatry, University of Kansas School of Medicine-Wichita and chief science officer for KUSM-W Clinical Trials Unit, told Medscape Medical News that drawing blood 24 hours after taking the drug can help determine the patient’s clearance of the drug.

"If the level is too low, either the patient is not taking the drug at all, or is taking too little, or is a rapid metabolizer, so the dose may have to be adjusted," said Preskorn, who was not involved in developing the consensus statement.

This is also an opportunity to initiate a conversation with patients regarding adherence, explaining that a low blood level will not have a therapeutic effect, discussing whether the patient has been taking the medication as prescribed, and addressing reasons for nonadherence, said Preskorn.

"We want to make it clear that clinicians should treat the patient, not the blood level," said Schoretsanitis.

"If a person is tolerating and responding to medications well, but we measure and see something unexpected, such as low levels, this doesn’t mean we need to adjust the dose merely because the levels are low," he added.

"Timing is very important" when measuring blood levels. For example, if a patient’s blood is usually tested in the morning but then is tested in the afternoon, he or she may exhibit a lower blood level, which may be reflective of the timing of the test rather than drug response.

"This statement is long overdue because TDM is probably the most underutilized tool in psychiatry for individualizing pharmacotherapy," said Preskorn.

Also commenting on the consensus statement for Medscape Medical News, Jonathan Meyer, MD, clinical professor of psychiatry, University of California, San Diego, said it brings attention to some of the key issues associated with  antipsychotic plasma monitoring and shows TDM is a valuable decision-making tool.

Meyer, who was not involved developing the document, pointed out that it may be difficult to obtain levels on newer antipsychotics, which require specialized labs that are not widely available and sometimes take up to 2 weeks to get results.

In such cases, physicians will have to rely on their best clinical judgment to manage an inadequate response until TDM results are available.

No commercial organizations had any role in funding the statement. Schoretsanitis has disclosed no relevant financial relationships. The other authors' disclosures are listed on the original paper. Meyer reports having received speaking or advising fees in the prior 12 months from Acadia Pharmaceuticals, Alkermes, Allergan (now AbbVie), Intra-Cellular Therapies, Janssen Pharmaceutica, Neurocrine, Otsuka America Inc, Sunovion Pharmaceuticals, and Teva Pharmaceutical Industries Ltd. Preskorn reports having been an investigator and/or a consultant to more than 140 pharmaceutical, biotechnology, diagnostic, and device companies and to the US Food and Drug Administration (FDA) and other federal agencies.

J Clin Psychiatry. Published online May 19, 2020. Consensus Statement

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